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DOI:10.1017/S0033291713000883

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Citation for published version (APA):Stone, J. M., Fisher, H. L., Major, B., Chisholm, B., Woolley, J., Lawrence, J., ... Young, A. H. (2014). Cannabisuse and first-episode psychosis: relationship with manic and psychotic symptoms, and with age at presentation.Psychological medicine, 44(3), 499-506. https://doi.org/10.1017/S0033291713000883

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Download date: 10. Sep. 2020

1

Cannabis use and first-episode psychosis – relationship to

manic and psychotic symptoms, and to age at presentation

Running Title: Cannabis and first-episode psychosis

James M Stone, Clinical Senior Lecturer, BSc. MBBS MRCPsych PhD (1)*

Helen L Fisher, MRC Population Health Scientist, BSc MSc PhD CPsychol AFBPsS (2)

Barnaby Major, Consultant Psychiatrist, BSc MBBS MRCPsych MSc (3)

Brock Chisholm, Principal Clinical Psychologist, DClinPsych (4)

James Woolley, Consultant Psychiatrist, BSc. MBBS MRCP MRCPsych (4)

Jo Lawrence, Clinical Services Leader, MSc (5)

Nikola Rahaman, Consultant Psychiatrist, MBBS MRCPsych (6)

John Joyce, Consultant Psychiatrist, MB BAO BCh MRCPsych (7)

Mark Hinton, Consultant Clinical Psychologist MSc (8)

Sonia Johnson, Professor of Social & Community Psychiatry, BA BM BCh MSc MRCPsych DM

(8)

Allan H Young, Professor of Psychiatry MB ChB MPhil PhD FRCPC FRCPsych (1)

on behalf of the MiData Consortium.

(1) Imperial College London, and West London Mental Health Trust, UK

(2) King's College London Institute of Psychiatry, UK

(3) EQUIP, East London NHS Foundation Trust, London, UK

(4) Wandsworth EIS, South West London & St. George’s Mental Health NHS Trust, London, UK

(5) Southwark EIS, South London & Maudsley NHS Foundation Trust, London, UK

(6) Kensington, Chelsea & Westminster EIS, Central & North West London NHS Foundation Trust,

London, UK

(7) Lewisham EIS, South London and Maudsley NHS Foundation Trust, London, UK

(8) University College London and Camden and Islington NHS Foundation Trust, UK

*corresponding author

email: james.m.stone@imperial.ac.uk

tel: 020 7594 7087

E517

Burlington Danes Building

Hammersmith Hospital

Du Cane Road

London

W12 0NN

Funding Sources: Nil

2

Background. Cannabis use has been reported to be associated with an earlier onset of symptoms in

patients with first-episode psychosis, and a worse outcome in those who continue to take cannabis.

In general, studies have concentrated on symptoms of psychosis rather than mania. In this study,

using a longitudinal design in a large naturalistic cohort of patients with first-episode psychosis, we

investigated the relationship between cannabis use, age of presentation to services, daily

functioning, and positive, negative and manic symptoms.

Method. Clinical data on 502 patients with first-episode psychosis was collected using the MiData

audit database from 7 London-based Early Intervention in psychosis teams. Individuals were

assessed at 2 time points – at entry to the service and after 1 year. On each occasion, Positive and

Negative Syndrome Scale, Young Mania Rating Scale, and Global Assessment of Functioning scale

disability subscale were rated. At both time-points, the use of cannabis and other drugs of abuse in

the 6 months preceding each assessment was recorded.

Results. Level of cannabis use was associated with a younger age at presentation, and manic

symptoms and conceptual disorganisation, but not with delusions, hallucinations, negative

symptoms or daily functioning. Cannabis users who reduced or stopped their use following contact

with services had the greatest improvement in symptoms at 1 year compared to continued users and

non-users. Continued users remained more symptomatic than non-users at follow-up.

Conclusions. Effective interventions for reducing cannabis use may yield significant health benefits

for patients with first-episode psychosis.

Key words: Cannabis, Schizophrenia, Bipolar Affective Disorder, Mania, Psychosis

3

Introduction

There is growing evidence that cannabis use may increase the risk of developing schizophrenia

(Manrique-Garcia et al 2012, Murray et al 2007), and that individuals with first-episode psychosis

with a history of cannabis use have an earlier onset of psychotic symptoms and younger age at

presentation to services (Gonzalez-Pinto et al 2011, Large et al 2011). Cannabis use has generally

been reported to be associated with increased positive symptoms and increase in risk of relapse in

patients with schizophrenia, with functional and symptomatic improvements reported to occur on

discontinuation (Faber et al 2012, Foti et al 2010, Grech et al 2005, Kuepper et al 2011, Zammit et

al 2008). Cannabis use has also been shown to affect mood (Henquet et al 2006), being reported to

be associated with depressive symptoms and worse outcome in individuals with bipolar affective

disorder (Strakowski et al 2007, van Rossum et al 2009). To our knowledge, no longitudinal studies

have yet examined the relationship of cannabis use to symptoms of mania in patients with first-

episode psychosis.

In this study, we examined the temporal relationship of cannabis use to manic and psychotic

symptoms and to age at presentation to services in a large UK-based cohort of patients with first-

episode psychosis. We hypothesized that cannabis use would be associated with a younger age of

presentation to services, and that cannabis use would be associated with a greater level of manic and

psychotic symptoms and with poorer daily functioning. We also hypothesized that reducing or

stopping cannabis use following the first psychotic episode would be associated with better

symptomatic and functional improvement.

Method

Ethical approval for this study was obtained from Wandsworth Research Ethics Committee. The

study was conducted in accordance with the ethical standards laid down in the Declaration of

Helsinki (1964, 2000). Clinical data were collected using the MiData audit database from 7

London-based Early Intervention in psychosis (EI) teams, covering the London boroughs of Brent,

4

Camden, City and Hackney, Islington, Kensington and Chelsea, Lewisham, Southwark,

Wandsworth, and Westminster (Fisher et al 2008, Ghali et al 2012). Within each team, clinicians

(doctors and care-coordinators) completed training by HLF over a 4 1/2 hour session, including

vignettes, practice sessions, and discussion of standardised ratings, and were required to

demonstrate high reliability with expert raters (Fisher et al 2008). In keeping with standard practice

in UK for first-episode psychosis teams, patient inclusion was based on a history of psychotic

symptoms that lasted for more than 7 days. Individuals who only experienced psychotic symptoms

during acute drug intoxication were not included in the study, but otherwise no prior assumptions

were made about the cause or diagnosis of the psychotic illness. Individuals were assessed at 2 time

points – at entry to the service and after 1 year in contact with the service. On each occasion,

Positive and Negative Syndrome Scale (PANSS) (Kay et al 1987), Young Mania Rating Scale

(YMRS) (Young et al 1978), and Global Assessment of Functioning scale disability subscale (GAF-

d) (Endicott et al 1976), were rated. At both time-points, the use of cannabis and other drugs of

abuse in the 6 months preceding each assessment was recorded using the combined Alcohol and

Drug Use scales (Drake et al 1996). Each drug was rated by clinicians on an operationalized 4-point

scale (No Use, Use, Abuse, Dependence), as previously described (Drake et al 1996). On this scale,

Use is defined as substance use with no evidence of persistent or recurrent social, occupational,

psychological or physical problems related to use, and no evidence of recurrent dangerous use.

Abuse is defined as substance use with the presence of any of these features. Dependence is defined

as the criteria for Abuse, plus at least 3 of the following 7 items: 1) Much time is spent obtaining or

using the substance; 2) Frequent intoxication or withdrawal interferes with other activities; 3)

Important activities are given up because of substance use; 4) Continued use despite knowledge of

substance-related problems; 5) Marked tolerance; 6) Characteristic withdrawal symptoms; 7) The

substance is used to relieve or avoid withdrawal problems. At the second time point, clinical

diagnosis and compliance with medication (where known) was also recorded.

5

Statistical analyses were completed using R version 2.14.1 (Ihaka and Gentleman 1996). We

generated a linear model with age at presentation to services as the dependent variable, and level of

cannabis use, alcohol use, nicotine use, cocaine use, and stimulant use in the preceding 6 months,

gender, ethnicity, social functioning (GAF-d) and symptoms at presentation (PANSS total and

YMRS) as independent variables. We then generated four separate linear models with baseline

YMRS, PANSS positive (PANSS-P), PANSS negative (PANSS-N) and GAF-d scores as dependent

variables and level of cannabis use, alcohol use, nicotine use, cocaine use, and stimulant use in the

preceding 6 months, age at presentation, gender and ethnicity as independent variables. In each

case, models were simplified using an Akaieke information criterion (AIC)-based stepwise method

implemented in R (Ihaka and Gentleman 1996). Where cannabis was significantly related to the

dependent variable in each ANOVA, we performed post-hoc Pearson's correlations on the level of

cannabis use vs. the dependent variable, uncorrected for independent variables.

In the follow-up sample, we compared baseline demographics and clinical measures with the full

(baseline only) sample using student's t-test and chi squared test, where appropriate. We used four

repeated measures ANOVAs to compare YMRS, PANSS (positive and negative) and GAF-d ratings

at baseline and follow-up in 3 groups based on their change in cannabis use over the period of study

– 1) patients who reported no cannabis use both at presentation and 1 year follow-up (“abstinent”),

2) patients who reported a reduction or a discontinuation of their use of cannabis (“reduced”), 3)

patients who reported a continuation or increase in their use of cannabis (“continued”). For all

analyses, histogram and qq plots of residuals were used to confirm normality of data and two-tailed

p values were employed to determine statistical significance.

Results

6

Baseline data on recent cannabis, cocaine, stimulant and alcohol use was available in 502 first-

episode patients (320 male, 182 female). Demographic and clinical details are summarized in Table

1. Age at presentation was predicted by a model driven primarily by level of cannabis use in the

preceding 6 months (associated with a younger age of presentation; post-hoc, uncorrected r = 0.18;

n = 502; p = 5 x 10-5) but also including level of alcohol use (associated with an older age at

presentation) and ethnicity (see Table 2). PANSS-P scores were predicted by a model primarily

driven by level of cannabis use (post-hoc, uncorrected r = 0.16; n = 502; p = 0.0004), but also

including nicotine use, age and gender (Table 3). YMRS scores were predicted by a model that

simplified to include level of cannabis use only (F(1,500) = 16.67; r = 0.18; n = 502; p = 5.2 x 10-5).

PANSS-N scores were predicted by a model including alcohol use and gender (Table 4). GAF-d

scores were predicted by a model including nicotine use and gender (Table 5).

Post-hoc analyses of individual PANSS-P and YMRS components revealed that level of cannabis

use was associated at presentation with increased conceptual disorganisation, excitement and

hostility on PANSS-P; and with elevated mood and increased motor activity, sexual interest,

irritability, speech – rate and amount, language – thought disorder, and disruptive – aggressive

behaviour on YMRS (all p values < 0.005; n = 502). Of note, cannabis use at presentation was not

associated with a significantly greater severity of hallucinations (p = 0.47) or delusions (p = 0.25).

At one year follow-up, data on cannabis use in 271 first-episode patients was available (54% of

baseline sample). Of these, 143 (53%) were non-users of cannabis both at baseline and at follow-up

(“abstinent” group), 80 (30%) were cannabis users at baseline but had stopped at follow-up

(“reduced” group), and 48 (17%) had either continued or increased their level of cannabis use from

baseline to follow-up (“continued” group). Out of the 271 first-episode patients with follow-up data,

221 (81%) had a diagnosis of schizophrenia or schizophreniform psychosis, 27 (10%) had a

diagnosis of bipolar affective disorder, 13 (5%) had a diagnosis of depressive psychosis, and in 10

(4%), the diagnosis was not recorded. Of those with a final diagnosis of bipolar affective disorder, 9

(34%), and 7 (26%) were classified as being cannabis abusers and cannabis users, respectively, at

7

baseline. In terms of medication concordance, 163 (60%) patients were recorded as being compliant

with medication, 19 (7%) as non-compliant, and in 89 (33%) patients, this information was not

available. The sample with baseline and follow-up data did not differ from the full (baseline-only)

sample in terms of age (t = 0.91, p = 0.36), gender (chisq = 1.16, p = 0.28), ethnicity (chisq = 3.415,

p = 0.64), PANSS-P (mean[SD] = 19.1[7.7]; t = 1.55, p = 0.121), PANSS-N (mean[SD] =

17.27[8.6], t = 1.01, p = 0.31), YMRS (mean[SD] = 10.8[9.6], t = 0.64, p = 0.52), GAF-d

(mean[SD] = 48.9, t = 1.86, p = 0.62), or cannabis use (t = 1.07, p = 0.28), at presentation.

ANOVA revealed a significant within-subjects effect of time for PANSS-P (F(1,268) = 163; n =

271; p < 0.0001), PANSS-N (F(1,268) = 63.6; n = 271; p < 0.0001), YMRS (F(1,268) = 87.3; n =

271 p < 0.0001) and GAF-d (F(1,268) = 136; n = 271 p<0.0001) with an improvement in all rating

scales between baseline and follow-up (mean[SD] PANSS-P = 12.2[6.4]; PANSS-N = 12.9[7.2];

YMRS = 4.7[6.9]; GAF-d = 64.0[17.6]; n = 271). There was a significant interaction between

change in cannabis use (“abstinent”, “reduced”, “continued”) and time for PANSS-P (F(2,268) =

9.93; n = 271; p < 0.0001; Figure 1), YMRS (F(2,268) = 9.39; n = 271 p = 0.0001; Figure 2), and

GAF-d (F(2,268) = 6.24; n = 271; p = 0.002; Figure 3). There was no significant interaction

between change in cannabis use and time for PANSS-N (F(2,268) = 2.65, p = 0.07). Compared to

individuals in the “continued” group for cannabis use, those in the “abstinent” and “reduced”

groups had lower PANSS-P (t = 3.26, 3.77; p = 0.001, 0.0003), YMRS (t = 2.4 3.57; p = 0.02,

0.0007) and GAF-d scores (t = 3.0, 3.66; p = 0.004, 0.0004) at follow-up. Medication concordance

was not found to differ with different patterns of cannabis use (90% concordance reported in the

“abstinent” group, 90% in the “reduced” group and 86% in the “continued” group, n = 102, 50, 30

respectively; Chisq = 0.32, p = 0.85).

Discussion

In keeping with previous studies, these data suggest cannabis use is associated with a younger age

of presentation to services (Gonzalez-Pinto et al 2011, Large et al 2011), and that discontinuation or

reduction of cannabis use is associated with enhanced symptomatic improvement in patients with

8

first-episode psychosis (Faber et al 2012, Foti et al 2010, Grech et al 2005, Kuepper et al 2011,

Zammit et al 2008).

In contrast, several recent studies of cannabis use in schizophrenia suggest that change in cannabis

use may not affect symptomatology to such a great extent. Three studies failed to demonstrate any

change in PANSS positive scores with reduction or discontinuation of cannabis, although in all of

these studies, discontinuation was associated with improvement in social functioning

(Barrowclough et al 2011, Faber et al 2012, Gonzalez-Pinto et al 2011). Another study found that,

although there was no difference in clinical measures between cannabis users and non-users,

cannabis users had more frequent hospital admissions (van Dijk et al 2012). A further group

reported that individuals who continued to take cannabis were more likely to be compliant with

medication, but, after correcting for this, cannabis users had higher levels of psychopathology

compared to those who discontinued cannabis (Faridi et al 2012). Thus, although positive

symptoms, as rated by PANSS, are not always associated with cannabis use in patients with

schizophrenia and first-episode psychosis, all studies have reported an improvement in functioning

with reduction in use. It is also clear that cannabis use may have a complex inter-relationship with

medication concordance in some patients, although this did not appear to be an issue in the present

study. It is interesting to note, although we found that cannabis did have an effect on PANSS

positive scores in the present study, that this effect was primarily driven by aggression and

disinhibition, rather than the more usually associated symptoms of delusions and hallucinations. It

is possible that the effects of cannabis reduction on illness outcome may be most marked in patients

with first-spisode psychosis. A recent meta-analysis found that reducing substance intake led to

improvements in symptomatology, but that this effect was only present in patients with first-episode

psychosis. In patients with more established illness, improvements were not statistically significant

(Mullin et al 2012).

Although other studies have found that cannabis use is associated with increases in positive affect

(self-rated reports of happiness, cheerfulness, relaxation, enthusiasm and satisfaction) in the general

9

population (Henquet et al 2006), and that it can worsen outcome in bipolar disorder (Strakowski et

al 2007, van Rossum et al 2009), our study is the first report, to our knowledge, of cannabis use

being associated more closely with manic-type symptoms than with hallucinations and delusions in

patients with first-episode psychosis.

Our finding of an association between cannabis use and a younger age of presentation to services is

in keeping with current evidence that cannabis use may lead to an earlier onset of psychotic

symptoms (Large et al 2011). It is possible that individuals with earlier and more severe symptoms

may be drawn to take cannabis for other reasons, or that younger individuals may simply be more

likely to have taken cannabis in the preceding 6 months due to cannabis use being more prevalent in

a younger age group. However, a recent meta-analysis concluded that these possibilities could not

fully explain the association between cannabis use and earlier onset of psychosis (Large et al 2011).

It should be noted that the 6 months prior to contact with services may have coincided with the

onset of prodromal symptoms, and we cannot exclude the possibility that cannabis was used in an

attempt to self-medicate.

It is interesting to note that, in the present study, the level of PANSS-P scores at baseline were

associated with nicotine use (at trend level) and with age, and that lower GAFd scores at baseline

were also associated with nicotine use. Previous studies have reported an association between

nicotine use and a greater severity of positive symptoms, as well as lower social functioning, in

patients with first-episode psychosis and schizophrenia (Krishnadas et al 2012, Zhang et al 2012).

Although the reasons for these associations have not been ascertained, it is possible that nicotine use

may worsen symptoms and levels of disability, or may be used as self-medication in an effort to

improve some aspects of functioning in the most unwell patients (Krishnadas et al 2012, Zhang et

al 2012). The reason for our finding of an association between age and symptoms in this study is

not known, but it is possible to speculate that older individuals were more likely to have been living

away from home, with less daily contact from family members, and so their illness may have

become more severe before being recognised.

10

We also found an association between alcohol use and less severe negative symptoms and between

male gender and more severe negative symptoms. The finding of an association (albeit weak)

between alcohol use and less severe PANSS-negative scores, has not been previously reported, to

our knowledge, and may simply reflect the fact that individuals with lower negative symptoms are

more capable of getting access to alcohol. The finding that male gender was associated with

PANSS-negative scores has been established for many years (Abel et al 2010, Andreasen 1982).

There are limitations to this study – most notably that cannabis and other drug use data were

dependent on patient recall and disclosure – the alcohol and drug use scales are self-report scales.

Furthermore, the data were recorded by a variety of different psychiatric team members who were

not blind to treatment status, though all had received the same training. Only 27 patients were

diagnosed with bipolar affective disorder at follow-up; therefore, manic-type symptoms, although

associated with cannabis use, were unlikely to have been the primary presenting complaint in the

majority of cases. Data on cannabis use at follow-up was not available in approximately 46% of the

original sample. This was because follow-up assessments were abbreviated in some instances, with

recordings of substance use being omitted, due to time pressures on the clinical teams involved in

the study. Although the baseline demographics and clinical measures in patients with substance use

data at both time points did not differ significantly from those with data from the first time point

only, it is possible that the longitudinal analysis may not be fully representative of the total study

population.

Despite these limitations, the findings from this study are derived from a relatively large naturalistic

cohort with a good coverage of different London teams and regions and so should be generalisable

to other inner city services in the UK. This study suggests that efforts to identify effective

interventions for reducing cannabis use are likely to yield significant health benefits for patients

with first-episode psychosis.

11

Contributors

SJ and HLF were involved in designing and implementing the MiData database. HLF conducted

MiData training with all of the clinicians and completed the merger of the teams’ datasets. BM, BC,

JW, JL, NR, JJ, MH and SJ contributed to collecting data from their respective Trusts. JMS

performed the analysis of the data and wrote the first draft of the manuscript. All authors

contributed to and have approved the final manuscript.

Conflict of Interest

AHY has received research grants, honoraria for educational activities and fees for consultancy

services from a number of pharmaceutical companies (AstraZeneca, BCI Pharma, Bristol-Myers

Squibb, Eli Lilly, GlaxoSmithKline, Janssen, Novartis, Otsuka Pharmaceutical Co., Pfizer, Sanofi-

Aventis, Servier Laboratories, Wyeth). JMS has received a non-restricted academic fellowship from

GlaxoSmithKline, and honoraria from Roche, AstraZeneca, Behrenberg Bank, and Pfizer. The

authors declare no conflict of interest.

Acknowledgements

Initial pilot work within Camden and Islington EIS was supported by Islington PCT. We are

extremely grateful to clinicians and patients from the teams participating as part of the MiData

Consortium for their time and enthusiasm: Camden & Islington EIS, EQUIP, STEP, Lewisham EIS,

Wandsworth EIS, Kensington, Chelsea & Westminster EIS, and Brent EIS.

12

Table 1: Demographic and baseline clinical details of EIS psychosis patients.

Demographic or clinical variable N (%) or M (SD)

Age 23.7 (4.9)

Gender (M/F) 320 (64) /182 (36)

Ethnicity (Caucasian/ Mixed/ Asian/ AC/

Chinese/ Other)

170 (34)/ 43 (9)/ 71 (14)/ 192 (38)/ 24 (5)/ 2 (0)

Education level (no qualifications/ GCSE/ A-

Level/ HND or professional qualification/

university but did not complete/ degree/

postgraduate/ other)

107 (21)/ 145 (29)/ 59 (12)/ 22 (4)/ 74 (15)/ 49

(10)/ 9 (2)/ 37 (7)

Employment status (unemployed/ student/ part-

time/ full-time/ other)

287 (57)/ 104 (21)/ 37 (7)/ 44 (9)/ 30 (6)

Cannabis use (no use/ use/ abuse/ dependence) 295 (59)/ 95 (19)/ 94 (19)/ 18 (4)

Alcohol use (no use/ use/ abuse/ dependence) 201 (40)/ 252 (50)/ 46 (9)/ 3 (1)

Nicotine use (no use/ use/ abuse/ dependence) 279 (56)/ 164 (33)/ 13 (3)/ 46 (9)

Cocaine use (no use/ use/ abuse/ dependence) 449 (89)/ 39 (8)/ 10 (2)/ 4 (1)

Stimulant use (no use/ use/ abuse/ dependence) 477 (95)/ 19 (4)/ 5 (1)/ 1 (0)

PANSS total 72.0 (24.6)

PANSS positive 18.2 (7.8)

PANSS negative 16.6 (8.3)

YMRS 10.3 (10.1)

GAF-D 51.3 (17.7)

AC – Black African and African-Caribbean, GCSE – General Certificate of Secondary Education. A-level: Advanced-

Level General Certificate of Education. HND – Higher National Diploma. PANSS – Positive and Negative Syndrome

Scale. YMRS – Young Mania Rating Scale. GAF-d – Global Assessment of Functioning scale – disability subscale, SD,

standard deviation.

13

Table 2: Components of general linear model predicting age at presentation.

Estimate Std. Error t value p

(Intercept) 25.5 3.33 7.66 9.5 x 10-14

Cannabis use -1.18 0.26 -4.55 6.8 x 10-6

Alcohol use 1.13 0.37 3.06 0.002

Ethnicity (Caucasian) -1.89 3.35 -0.57 0.57

Ethnicity (Mixed) -3.28 3.40 -0.96 0.34

Ethnicity (Asian) -0.11 3.37 -0.032 0.97

Ethnicity (AC) -2.17 3.34 -0.65 0.52

Ethnicity (Chinese) -1.10 3.46 -0.32 0.75

F(7,494) = 5.69; p = 2.4 x 10-06. AC - Black African and African-Caribbean.

Table 3: Components of general linear model predicting PANSS-positive scores at

presentation.

Estimate Standard Error t value p

(Intercept) 12.6 1.87 6.74 4.5 x 10-11

Cannabis use 1.12 0.43 2.61 0.0094

Nicotine use 0.73 0.41 1.76 0.079

Age 0.16 0.07 2.16 0.032

Gender (Male) 1.03 0.73 1.41 0.16

F(3,498) = 5.76; p = 0.0002. PANSS – Positive and Negative Syndrome Scale.

Table 4: Components of general linear model predicting PANSS-negative scores at

presentation.

Estimate Standard Error t value p

(Intercept) 16.62 0.70 23.75 2 x 10-16

Alcohol use -1.30 0.56 -2.48 0.013

Gender (Male) 1.55 0.77 2.02 0.044

F(2,499) = 4.634; p = 0.01. PANSS – Positive and Negative Syndrome Scale.

14

Table 5: Components of general linear model predicting GAF-d scores at presentation

F(2,499) = 3.954; p = 0.01. GAF-d – Global Assessment of Functioning scale – disability subscale

Estimate Standard Error t value p

(Intercept) 54.2 1.37 39.69 2 x 10-16

Nicotine use -1.74 0.87 -2.00 0.046

Gender (Male) -2.74 1.65 -1.66 0.097

15

Figure 1: Interaction plot of the positive subscale of the Positive and Negative Syndrome Scale

(PANSS-P) over time. Figure shows PANSS-P in patients with first-episode psychosis who

reported no cannabis use both at presentation and 1 year follow-up (Abstinent), who reported a

reduction or a discontinuation of their use of cannabis (Reduced), and who reported a continuation

or increase in their use of cannabis between baseline and follow-up (Continued). Error bars show

Standard Error of Mean.

16

Figure 2: Interaction plot of Young Mania Rating Scale (YMRS) over time. Figure shows

YMRS in patients with first-episode psychosis who reported no cannabis use both at presentation

and 1 year follow-up (Abstinent), who reported a reduction or a discontinuation of their use of

cannabis (Reduced), and who reported a continuation or increase in their use of cannabis between

baseline and follow-up (Continued). Error bars show Standard Error of Mean.

17

Figure 3: Interaction plot of the Global Assessment of Functioning scale - disability subscale

(GAF-d) over time. Figure shows GAF-d in patients with first-episode psychosis who reported no

cannabis use both at presentation and 1 year follow-up (Abstinent), who reported a reduction or a

discontinuation of their use of cannabis (Reduced), and who reported a continuation or increase in

their use of cannabis between baseline and follow-up (Continued). Error bars show Standard Error

of Mean.

18

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